Stroke is a leading cause of morbidity and mortality in aging western populations. The causes of stroke are multiple, with most falling into a category of “cryptogenic” etiology. Most of these cryptogenic events are felt to be related to atheroma at the carotid bifurcation and atheroembolus to the ipsilateral cerebral hemisphere. There is much pathological evidence to support this supposition; however, clearly definitive evidence of the hypothesis will never be essentially achievable at the present limits of imaging technology due to the physical limitations of current, state-of-the-art nondestructive anatomical imaging.
Carotid atheroma is nonetheless felt to be the most important source of stroke. Historically, removing a risky plaque through surgical carotid Endarterectomy has been proven to improve outcomes via a randomized controlled trial: the NASCET. In this historical study, the risk due to plaque was determined by the finding of lumenographic severe stenosis and proxy markers for this angiographic finding. Thus, an imaging based, somewhat subjective medical assessment of lumenographic severe stenosis (70-99% narrowed) is currently the mainstay logic behind the medical decision to proceed with or withhold the only proven surgical treatment for the culprit atherosclerotic lesion: carotid endarterectomy. The patients identified with severe stenosis are either symptomatic (having a history of TIA/stroke) or asymptomatic from their carotid bifurcation plaque, and surgical decision making has evolved to incorporate this data into the clinical decision making risk model. The goal of this procedure of endarterectomy is to excise the dangerous atheroma at the carotid bifurcation safely.
Lumenographic imaging has significant limitations. Via these methods, the blood pool within a vessel is imaged and the thickness and geometry of the vessel wall is inferred/imagined by an imaging expert. The finding of “severe stenosis” has become the driving logic behind this imaging technique. The mathematical definition of this term is imprecise and based ultimately on a subjective interpretation of where the vessel adventitial surface lies (the extreme outer wall of the vessel, or, anatomically what is known as the vascular adventitial layer). The thickening of the vessel wall, from outermost adventitia to innermost endothelium is inferred from the geometry of the lumen. Stenosis is best and most widely understood as the geometrical narrowing of a 2-d projection of the blood pool transversely to the axis of the vascular flow vector.
Patients with 60-69% stenosis who are symptomatic may be offered additional antiplatelet adhesion medications which are felt, on aggregate, to reduce their risks for further events.
Concurrently developing with the previously described surgical and medical decision model, a model atherosclerosis lesion progression and regression has been developed in part by the American Heart Association based on histopathology and cadaver studies. The model is inherently based on destructive pathological imaging, thus, it is inherently limited in its extent of application. This model identifies the Type VI plaque as one that is directly associated with atheroembolism. By definition, this type of plaque displays “disruption of the lesion surface, hematoma or hemorrhage, and thrombotic deposits.” Circulation. 1995; 92:1355-1374 doi: 10.1161/01.CIR.92.5.1355 (Circulation. 1995; 92:1355-1374.)® 1995 American Heart Association, Inc. A Definition of Advanced Types of Atherosclerotic Lesions and a Histological Classification of Atherosclerosis—A Report From the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Herbert C. Stary, MD, CHAIR; A. Bleakley Chandler, MD; Robert E. Dinsmore, MD; Valentin Fuster, MD, PhD; Seymour Glagov, MD; William Insull, Jr, MD; Michael E. Rosenfeld, PhD; Colin J. Schwartz, MD; William D. Wagner, PhD; Robert W. Wissler, PhD, MD.
Conceivably, these three markers would be optically visible from the lumen of the vessel if the blood pool was cleared of blood transiently and an optical scope was to effectively sample the region of the carotid bifurcation using traditional reflected light anatomical-optical data as well as transilluminated anatomical-optical data and with sufficient detail. These images could secure the diagnosis of Type VI atheroma independent of the presence of stenosis. This would provide a logical and clinically applicable manner in which to medically assess the risk of stroke due to vulnerable or active atherosclerotic disease. If there is a surface tear, ulcer, thrombus in situ, and/or hemorrhage into the wall of the vessel, the plaque is unstable and is capable of throwing a clot downstream to the brain at any time. This is specifically the very valuable clinical information that this device will provide.
Imaging based enterprises to blend the pathologically based models to nondestructive imaging based models of discrete atherosclerotic lesions have been ongoing and present an opportunity to better understand and treat carotid atheroma. The carotid bifurcation presents a uniquely patterned region for atheroma development and risk.
Atherosclerosis is a systemic disease affecting the entire arterial vascular system. The device will allow study of this specific disease in a number of locations where the disease may be present, including the coronary arteries, renal arteries, splanchnic arteries and extremity arteries.
Additional optical imaging study of the carotid bifurcation and other endovascular positions could be performed with the catheter using fluorescent optical probes that are designed to bind to cell surface receptors, cell surface molecules and extracellular materials that are important to disease such as fibrin or platelet aggregates. Through excitation of the marker probe fluorescence and detection and spatial localization of the fluorescence, sophisticated and nondestructive in-situ study of atherosclerosis will be enabled by the catheter.
Furthermore, the immediate benefits to society of better carotid bifurcation atherosclerotic disease characterization and the of monitoring of progression/regression of these critical atherosclerotic lesions will be great as medical treatments such as blood thinners of various design and endovascular plaque stabilization treatments such as stents and drug eluting balloon angioplasty are offered to patients with critical disease that was previously completely unrecognized.
In broader applications, optical imaging in the manner outlined above may inform research and development into a number of diseases including but not limited to Parkinson's disease, Alzheimer's disease and Multiple Sclerosis. In these three examples, the catheter assembly would be inserted directly into the brain tissue similarly to other electrodes and ventricular catheters that are surgically inserted through the brain tissue. Optical fluorescent marker molecular probes could be directly applied to the interstitial fluid of the brain via catheter sideholes, through the cerebrospinal fluid via lumbar or dural puncture, or, through the vascular system using a standard intravenous injection. The data obtained through nondestructive in-situ evaluation using molecular probes could lead to a better understanding of these disease processes. Currently, there is little robust pathophysiological information regarding the pathophysiology of these disease processes due to the inability to study the disease in vivo in humans at cellular and molecular levels of detail. The device is designed to enable these studies.
However, the immediate specific aim of the present invention is to identify and characterize critical disease at the carotid bifurcation in a clinically effective manner using technology that is currently enabled.